Shock is a common complication of severe febrile illness, and worldwide aggressive correction with intravenous bolus therapy is recommended as the initial treatment. Nevertheless, the evidence supporting this approach remains weak. The only controlled trial of fluid resuscitation, Fluid Expansion as Supportive Therapy (FEAST), involving 3141 African children with severe febrile illness, including large groups with sepsis and malaria, called into question aggressive fluid resuscitation, demonstrating excess mortality in both bolus arms (albumin and saline) compared to no-bolus control, relative risk of morality in bolus versus control was 1.45(1.13-1.86, p=0.003). Excess mortality was consistent across all subgroups, being greatest in those with the most severe forms of shock and acidosis. Remarkably, despite earlier shock reversal in those receiving fluid boluses the excess mortality in the FEAST trial was caused by subsequent cardiovascular collapse and was not secondary to fluid overload. These observations are intriguing warranting an in-depth understanding of host responses including those of the myocardium to fluid resuscitation and at the microvasacular level since the two maybe synergistic. Current studies are underway in ovine models of sepsis (‘FEAST-in-Sheep’) in Professor John Fraser’s laboratory, Brisbane to understand the mechanism of harm, gain further insights in host responses to fluid management, and re-define the optimal fluid and supportive inotrope/vasopressor management of septic shock. Four years have elapsed since the publication of FEAST, yet World Health Organization continues to recommend fluid boluses for children managed in resource-poor hospitals, where there is no access to intensive care. These are the precise settings where the FEAST trial was conducted in order to inform management guidelines. In Africa alone, where one in 10 febrile child admissions present with shock, we have estimated that the current guidelines, if fully implemented, will result in ~5,600 and 33,000 excess deaths each year per million hospital admissions treated for shock.

1. Fluids and Kids: What Now?
Kathryn Maitland
Imperial College, London

2. 1998
Fluid bolus therapy –my story

4. Glucose control
The Silent emergency
Simple treatments: evidence base?

5. Severe febrile illness: evidence of hypovolaemia?
Feature Valid (%) Fatality rate (%)
Airway and respiration:
Hypoxia (O2 Saturation <90%)
a
86/501 (17.1) 30
Respiratory rate >60
breaths/minute
83/501 (16.6) 20
Deep breathing 104/515 (20.2) 31
Cardiovascular and hydration:
Tachycardia (>160 beats/min) 81/503 (16.1) 17
Bradycardia (<80 beats/min) 5/503 (1) 40
Hypotension (<80mmHg) 66/507 (13) 26
Capillary refill ≥3secs 165/496 (33.3) 15
Sunken eyes 36/514 (7) 28
Decreased skin turgor 29/514 (5.6) 28
Neurological:
Convulsions 303/515 (58.8) 8.3
Prostration 353/514 (68.7) 13
Blantyre Coma Score ≤2 266/509 (52.3) 16
Laboratory:
Severe acidemia (pH <7.2) 96/436 (22) 36
Elevated creatinine (>80 mmols/L) 96/469 (20.4) 26
Hypoglycaemia (<2.5 mmols/L) 58/478 (12.1) 28
Hyperglycaemia (>10 mmols/L) 47/478 (9.8) 19
Hyperkalaemia (>5.5 mmols/L) 61/493 (12.3) 28
Hyponatraemia (<125 mmols/L) 21/493 (4.3) 14

6. Physiological and dose-finding studies
612121112125 4131516161611 498106106N =
Time(hrs)
4824126-841-20
CVP(cmH2O)
12
10
8
6
4
2
0
-2
CVP low at
admission
B
B=Bolus ~ 20-40mls/kg
Maitland et al Pediatr Crit Care (2005)

8. Forest Plot
Choice of fluids for resuscitation: a systematic review:
Akech et al BMJ 2010

9. Perpetual funding crisis….
Major concerns raised in grant reviews:
Shock:
•Provide the evidence (ie relevant physiological
research) from paediatric literature
underpinning shock definition
Management:
• Show us the evidence that on which the fluid
management recommendations are based

10. Fluid bolus therapy:
The Story from the Rest of the world
(paediatrics)

11. Paediatric recommendations
Dellinger Surviving Sepsis 2012

12. Paediatric Recommendations:
Dellinger 2012
‘…… blood pressure alone is not a reliable endpoint
for assessing the adequacy of resuscitation.
However, once hypotension occurs, cardiovascular
collapse may soon follow. Thus, fluid resuscitation is
recommended for both normotensive and
hypotensive children in hypovolemic shock [542–
554]’’.
4 dengue papers, 1 malaria systematic review;
implementation (before after study designs) one
small RCT (India)

13. International Evidence for Paediatric Fluid
resuscitation guideline
Guidelines FOR THE WHOLE WORLD based on 2 retrospective
analyses from one hospital (Pittsburgh; 3O
referral ICU)
Patient population : survivors to ICU admission: that were ventilated & inotrope
dependant
Endpoint/outcome: Retrospective review of shock reversal and volumes of fluid
required in the first hour on down stream endpoints – need for fluid boluses,
inotropes etc.
First study:
5 year review: 34 children with septic shock ~ 7 children/yr
>=40mls/kg initial fluid resuscitation (9 children) associated with better
outcome (Carcillo et al, JAMA 1991)
Recommmended as the standard of care following publication.

14. 9 children

15. International Evidence for Paediatric Fluid
resuscitation guideline
Second study:
10 year review of Septic shock (91 children) ~ 9 children/yr
Patient population : SURVIVED to ICU admission: ventilated &
inotrope dependant
Endpoint/outcome: Shock reversal by community physicians:
volumes of fluid required in the first hour
>60mls/kg over 15 mins (34 children): early reversal of shock improves
outcome; (Han Y et all, Pediatrics 2003)
Now recommended as the standard of care
Surviving Sepsis 2012 guideline graded 2C level of evidence
= Weak recommendation based on very poor evidence

16. 2007
The FEAST trial was funded!!!

17. Pragmatic trial
Severe malarial + acidosis
Undernutrition
Sepsis/shock
Cerebral malariaPneumonia
Meningitis/encephalitis
HIV
Severe malarial anaemia

18. Controlled trial of fluid resuscitation
(FEAST A)
Follow-up to 4 weeks (24 weeks if developed neurological sequelae by 4 weeks)
Clinical assessments at 1, 4, 8, 24, 48 hours and at 4 weeks
Impaired perfusion
Any one of:
•Cap refill > 2 secs,
•Severe tachycardia,
•temperature gradient
•weak pulse
Excluded: Gastroenteritis Severe malnutrition Non-medical admission (burns,trauma)

20. Primary endpoint: 48 hour mortality
10.5%
7.3%

21. Remarkable consistency of adverse outcome of boluses
.
.
.
.
.
.
Malaria:
positive
negative
Subtotal (I-squared = 0.0%, p = 0.691)
Coma:
comatose
not comatose
Subtotal (I-squared = 74.3%, p = 0.049)
Haemoglobin:
< 5 g/dL
>= 5 g/dL
Subtotal (I-squared = 2.9%, p = 0.310)
Base deficit:
>= 8 mmol/L
< 8 mmol/L
Subtotal (I-squared = 14.8%, p = 0.279)
Lactate:
> 5 mmol/L
<= 5 mmol/L
Subtotal (I-squared = 39.2%, p = 0.200)
Period:
before amendment
after amendment
Subtotal (I-squared = 0.0%, p = 0.498)
Subgroup
1.59 (1.10, 2.31)
1.43 (1.01, 2.04)
1.51 (1.17, 1.95)
1.04 (0.73, 1.49)
1.69 (1.21, 2.36)
1.40 (1.10, 1.79)
1.71 (1.16, 2.51)
1.31 (0.93, 1.84)
1.47 (1.14, 1.90)
1.68 (1.18, 2.39)
1.06 (0.50, 2.24)
1.54 (1.12, 2.13)
1.38 (1.05, 1.81)
2.17 (1.14, 4.14)
1.50 (1.17, 1.93)
1.38 (1.05, 1.83)
1.72 (0.98, 3.05)
1.45 (1.13, 1.86)
risk (95% CI)
Relative
110/1202
108/884
218/2086
78/317
143/1777
221/2094
101/655
114/1384
215/2039
128/740
20/659
148/1399
157/764
49/1225
206/1989
172/1691
49/406
221/2097
bolus
Events,
34/591
38/446
72/1037
33/140
43/904
76/1044
30/332
43/683
73/1015
34/330
10/350
44/680
59/395
11/597
70/992
62/844
14/200
76/1044
no bolus
Events,
1.59 (1.10, 2.31)
1.43 (1.01, 2.04)
1.51 (1.17, 1.95)
1.04 (0.73, 1.49)
1.69 (1.21, 2.36)
1.40 (1.10, 1.79)
1.71 (1.16, 2.51)
1.31 (0.93, 1.84)
1.47 (1.14, 1.90)
1.68 (1.18, 2.39)
1.06 (0.50, 2.24)
1.54 (1.12, 2.13)
1.38 (1.05, 1.81)
2.17 (1.14, 4.14)
1.50 (1.17, 1.93)
1.38 (1.05, 1.83)
1.72 (0.98, 3.05)
1.45 (1.13, 1.86)
risk (95% CI)
Relative
110/1202
108/884
218/2086
78/317
143/1777
221/2094
101/655
114/1384
215/2039
128/740
20/659
148/1399
157/764
49/1225
206/1989
172/1691
49/406
221/2097
bolus
Events,
bolus reduces risk bolus increases risk
.
.
.
.
.
.
Malaria:
positive
negative
Subtotal (I-squared = 0.0%, p = 0.691)
Coma:
comatose
not comatose
Subtotal (I-squared = 74.3%, p = 0.049)
Haemoglobin:
< 5 g/dL
>= 5 g/dL
Subtotal (I-squared = 2.9%, p = 0.310)
Base deficit:
>= 8 mmol/L
< 8 mmol/L
Subtotal (I-squared = 14.8%, p = 0.279)
Lactate:
> 5 mmol/L
<= 5 mmol/L
Subtotal (I-squared = 39.2%, p = 0.200)
Period:
before amendment
after amendment
Subtotal (I-squared = 0.0%, p = 0.498)
Subgroup
1.59 (1.10, 2.31)
1.43 (1.01, 2.04)
1.51 (1.17, 1.95)
1.04 (0.73, 1.49)
1.69 (1.21, 2.36)
1.40 (1.10, 1.79)
1.71 (1.16, 2.51)
1.31 (0.93, 1.84)
1.47 (1.14, 1.90)
1.68 (1.18, 2.39)
1.06 (0.50, 2.24)
1.54 (1.12, 2.13)
1.38 (1.05, 1.81)
2.17 (1.14, 4.14)
1.50 (1.17, 1.93)
1.38 (1.05, 1.83)
1.72 (0.98, 3.05)
1.45 (1.13, 1.86)
risk (95% CI)
Relative
110/1202
108/884
218/2086
78/317
143/1777
221/2094
101/655
114/1384
215/2039
128/740
20/659
148/1399
157/764
49/1225
206/1989
172/1691
49/406
221/2097
bolus
Events,
34/591
38/446
72/1037
33/140
43/904
76/1044
30/332
43/683
73/1015
34/330
10/350
44/680
59/395
11/597
70/992
62/844
14/200
76/1044
no bolus
Events,
1.59 (1.10, 2.31)
1.43 (1.01, 2.04)
1.51 (1.17, 1.95)
1.04 (0.73, 1.49)
1.69 (1.21, 2.36)
1.40 (1.10, 1.79)
1.71 (1.16, 2.51)
1.31 (0.93, 1.84)
1.47 (1.14, 1.90)
1.68 (1.18, 2.39)
1.06 (0.50, 2.24)
1.54 (1.12, 2.13)
1.38 (1.05, 1.81)
2.17 (1.14, 4.14)
1.50 (1.17, 1.93)
1.38 (1.05, 1.83)
1.72 (0.98, 3.05)
1.45 (1.13, 1.86)
risk (95% CI)
Relative
110/1202
108/884
218/2086
78/317
143/1777
221/2094
101/655
114/1384
215/2039
128/740
20/659
148/1399
157/764
49/1225
206/1989
172/1691
49/406
221/2097
bolus
Events,
bolus reduces risk bolus increases risk
In every subgroup and at each study site fluid boluses were harmful

22. Mortality Excess with Boluses by Shock Definition
FEAST ACCM
(cold,
2 signs)
PALS
2010
Comp
WHO/ETAT
Mortality
PALS
2010
With every definition of shock, boluses were
associated with increased mortality
NEJM Oct 2011
WHO/ETAT
Mortality
Bolus= 48%
Control=20%

23. .
.
.
.
.
.
.
.
.
C u t o f f a t 3 g
H b < 3 g / d l
H b > = 3 g / d l
S u b t o t a l ( I- s q u a r e d = 0 . 0 % , p = 0 . 4 5 0 )
C u t o f f a t 4 g
H b < 4 g / d l
H b > = 4 g / d l
S u b t o t a l ( I- s q u a r e d = 0 . 0 % , p = 0 . 3 3 5 )
C u t o f f a t 5 g
H b < 5 g / d l
H b > = 5 g / d l
S u b t o t a l ( I- s q u a r e d = 2 . 9 % , p = 0 . 3 1 0 )
C u t o f f a t 6 g
H b < 6 g / d l
H b > = 6 g / d l
S u b t o t a l ( I- s q u a r e d = 0 . 0 % , p = 0 . 7 7 0 )
C u t o f f a t 7 g
H b < 7 g / d l
H b > = 7 g / d l
S u b t o t a l ( I- s q u a r e d = 0 . 0 % , p = 0 . 6 3 1 )
C u t o f f a t 8 g
H b < 8 g / d l
H b > = 8 g / d l
S u b t o t a l ( I- s q u a r e d = 0 . 0 % , p = 0 . 7 2 2 )
C u t o f f a t 9 g
H b < 9 g / d l
H b > = 9 g / d l
S u b t o t a l ( I- s q u a r e d = 0 . 0 % , p = 0 . 7 9 2 )
C u t o f f a t 1 0
H b < 1 0 g / d l
H b > = 1 0 g /d l
S u b t o t a l ( I- s q u a r e d = 0 . 0 % , p = 0 . 5 4 7 )
C u t o f f a t 1 1
H b < 1 1 g / d l
H b > = 1 1 g / d l
S u b t o t a l ( I- s q u a r e d = 0 . 0 % , p = 0 . 8 0 1 )
S u b g r o u p
1 . 7 4 ( 1 . 0 2 , 2 . 9 9 )
1 . 3 8 ( 1 . 0 3 , 1 . 8 4 )
1 . 4 5 ( 1 . 1 3 , 1 . 8 7 )
1 . 7 4 ( 1 . 1 1 , 2 . 7 3 )
1 . 3 3 ( 0 . 9 8 , 1 . 8 1 )
1 . 4 5 ( 1 . 1 2 , 1 . 8 7 )
1 . 7 1 ( 1 . 1 6 , 2 . 5 1 )
1 . 3 1 ( 0 . 9 3 , 1 . 8 4 )
1 . 4 7 ( 1 . 1 4 , 1 . 9 0 )
1 . 4 1 ( 1 . 0 1 , 1 . 9 9 )
1 . 5 3 ( 1 . 0 4 , 2 . 2 3 )
1 . 4 7 ( 1 . 1 4 , 1 . 8 9 )
1 . 5 3 ( 1 . 1 1 , 2 . 1 3 )
1 . 3 5 ( 0 . 9 0 , 2 . 0 2 )
1 . 4 6 ( 1 . 1 3 , 1 . 8 8 )
1 . 4 3 ( 1 . 0 6 , 1 . 9 2 )
1 . 5 9 ( 0 . 9 7 , 2 . 5 8 )
1 . 4 7 ( 1 . 1 4 , 1 . 9 0 )
1 . 4 3 ( 1 . 0 8 , 1 . 9 0 )
1 . 5 7 ( 0 . 8 7 , 2 . 8 2 )
1 . 4 6 ( 1 . 1 3 , 1 . 8 8 )
1 . 5 0 ( 1 . 1 4 , 1 . 9 7 )
1 . 1 9 ( 0 . 6 0 , 2 . 3 8 )
1 . 4 5 ( 1 . 1 3 , 1 . 8 8 )
1 . 4 8 ( 1 . 1 4 , 1 . 9 3 )
1 . 3 1 ( 0 . 5 2 , 3 . 2 8 )
1 . 4 7 ( 1 . 1 4 , 1 . 8 9 )
r is k ( 9 5 % C I )
R e la t iv e
5 3 / 2 1 7
1 6 2 / 1 8 2 2
2 1 5 / 2 0 3 9
7 9 / 4 5 0
1 3 6 / 1 5 8 9
2 1 5 / 2 0 3 9
1 0 1 / 6 5 5
1 1 4 / 1 3 8 4
2 1 5 / 2 0 3 9
1 1 4 / 8 3 0
1 0 1 / 1 2 0 9
2 1 5 / 2 0 3 9
1 3 1 / 9 8 7
8 4 / 1 1 3 6
2 1 5 / 2 1 2 3
1 5 0 / 1 1 7 8
6 5 / 8 6 1
2 1 5 / 2 0 3 9
1 7 2 / 1 3 6 8
4 3 / 6 7 1
2 1 5 / 2 0 3 9
1 9 0 / 1 5 5 9
2 5 / 4 8 0
2 1 5 / 2 0 3 9
1 9 9 / 1 7 4 8
1 6 / 2 9 1
2 1 5 / 2 0 3 9
b o l u s
E v e n t s ,
1 4 / 1 0 0
5 9 / 9 1 5
7 3 / 1 0 1 5
2 1 / 2 0 8
5 2 / 8 0 7
7 3 / 1 0 1 5
3 0 / 3 3 2
4 3 / 6 8 3
7 3 / 1 0 1 5
4 0 / 4 1 2
3 3 / 6 0 3
7 3 / 1 0 1 5
4 3 / 4 9 7
3 0 / 5 4 8
7 3 / 1 0 4 5
5 3 / 5 9 5
2 0 / 4 2 0
7 3 / 1 0 1 5
5 9 / 6 7 3
1 4 / 3 4 2
7 3 / 1 0 1 5
6 2 / 7 6 3
1 1 / 2 5 2
7 3 / 1 0 1 5
6 7 / 8 7 2
6 / 1 4 3
7 3 / 1 0 1 5
n o _ b o l u s
E v e n t s ,
1 . 7 4 ( 1 . 0 2 , 2 . 9 9 )
1 . 3 8 ( 1 . 0 3 , 1 . 8 4 )
1 . 4 5 ( 1 . 1 3 , 1 . 8 7 )
1 . 7 4 ( 1 . 1 1 , 2 . 7 3 )
1 . 3 3 ( 0 . 9 8 , 1 . 8 1 )
1 . 4 5 ( 1 . 1 2 , 1 . 8 7 )
1 . 7 1 ( 1 . 1 6 , 2 . 5 1 )
1 . 3 1 ( 0 . 9 3 , 1 . 8 4 )
1 . 4 7 ( 1 . 1 4 , 1 . 9 0 )
1 . 4 1 ( 1 . 0 1 , 1 . 9 9 )
1 . 5 3 ( 1 . 0 4 , 2 . 2 3 )
1 . 4 7 ( 1 . 1 4 , 1 . 8 9 )
1 . 5 3 ( 1 . 1 1 , 2 . 1 3 )
1 . 3 5 ( 0 . 9 0 , 2 . 0 2 )
1 . 4 6 ( 1 . 1 3 , 1 . 8 8 )
1 . 4 3 ( 1 . 0 6 , 1 . 9 2 )
1 . 5 9 ( 0 . 9 7 , 2 . 5 8 )
1 . 4 7 ( 1 . 1 4 , 1 . 9 0 )
1 . 4 3 ( 1 . 0 8 , 1 . 9 0 )
1 . 5 7 ( 0 . 8 7 , 2 . 8 2 )
1 . 4 6 ( 1 . 1 3 , 1 . 8 8 )
1 . 5 0 ( 1 . 1 4 , 1 . 9 7 )
1 . 1 9 ( 0 . 6 0 , 2 . 3 8 )
1 . 4 5 ( 1 . 1 3 , 1 . 8 8 )
1 . 4 8 ( 1 . 1 4 , 1 . 9 3 )
1 . 3 1 ( 0 . 5 2 , 3 . 2 8 )
1 . 4 7 ( 1 . 1 4 , 1 . 8 9 )
r is k ( 9 5 % C I )
R e la t iv e
5 3 / 2 1 7
1 6 2 / 1 8 2 2
2 1 5 / 2 0 3 9
7 9 / 4 5 0
1 3 6 / 1 5 8 9
2 1 5 / 2 0 3 9
1 0 1 / 6 5 5
1 1 4 / 1 3 8 4
2 1 5 / 2 0 3 9
1 1 4 / 8 3 0
1 0 1 / 1 2 0 9
2 1 5 / 2 0 3 9
1 3 1 / 9 8 7
8 4 / 1 1 3 6
2 1 5 / 2 1 2 3
1 5 0 / 1 1 7 8
6 5 / 8 6 1
2 1 5 / 2 0 3 9
1 7 2 / 1 3 6 8
4 3 / 6 7 1
2 1 5 / 2 0 3 9
1 9 0 / 1 5 5 9
2 5 / 4 8 0
2 1 5 / 2 0 3 9
1 9 9 / 1 7 4 8
1 6 / 2 9 1
2 1 5 / 2 0 3 9
b o l u s
E v e n t s ,
b o lu s r e d u c e s r is k b o l u s in c r e a s e s r i s k
1. 2 5 . 5 1 2 4
Control betterBolus better
Hb 3 g/dl
Hb 11g/dl
Did anaemia affect outcome?
Each level of Haemoglobin level
Maitland BMC Medicine 2013

24. Sepsis: Culture +ve or
Goldstein et al definition (& malaria negative)
Maitland Unpublished

25. Acute Kidney Injury:
Evidence fluid challenge beneficial?
Maitland Unpublished
Period <8 hours 8-<24 hrs 24-<48 hrs 48 hrs – 28 days Total
Distribution of
deaths over time
50 31 12 15 108
% deaths with
BUN≥20 mg/dl
46% 29% 11% 14% 100%

27. Presenting syndromes

28. Response to fluid boluses

29. Shock reversal at one-hour&
:
does not predict benefit
Bolus combined No Bolus Total
¥
Relative risk*
No shock at
one hour 43/876 (5%) 8/323 (2%) 51/1198 (4%)
1.98
(0.94-4.17)
Continued
shock at one
hour 141/1180(12%) 50/701 (7%) 191/1881(10%)
1.67
(1.23-2.28)
&
One-hour time point chosen since no difference in deaths in
bolus vs control arms ie result not influenced by survivorship bias
*p-value for heterogeneity between the two relative risks. = 0.68

30. 1
1.5
2
2.5
3
3.5
4
4.5
5
5.5
6
6.5
7
Cumulativeincidence(%)
0 4 8 12 16 20 24 28 32 36 40 44 48
Hours until death
Cardiogenic (Bolus)
Cardiogenic (No Bolus)
Neurological (Bolus)
Neurological (No Bolus)
Respiratory (Bolus)
Respiratory (No Bolus)
Unknown/Other (Bolus)
Unknown/Other (No Bolus)
Percentage of death in Bolus (B) vs Control (C) with Terminal Clinical Event attributed to:
 Cardiogenic/shock: 4.6%(n=96) B vs 2.6%(n=27) C [Ratio 1.79 (1.17-2.74) p=0.008]
 Neurological: 2.1%(n=44) B vs 1.8%(n=19) C [Ratio 1.15 (0.67-1.98); p=0.6]
 Respiratory: 2.2%(n=47) B vs 1.3%(n=14) C [Ratio 1.68 (0.93-3.06); p=0.09]
‘Terminal Clinical Event’:
Cumulative incidence of mortality for bolus & control arms

31. Cup half full or half empty?

32. Dose –response?
.
.
.
Lactate:
> 5 mmol/L
<= 5 mmol/L
Subtotal (I-squared = 39.2%, p = 0.200)
Period:
before amendment
after amendment
Subtotal (I-squared = 0.0%, p = 0.498)
1.38 (1.05, 1.81)
2.17 (1.14, 4.14)
1.50 (1.17, 1.93)
1.38 (1.05, 1.83)
1.72 (0.98, 3.05)
1.45 (1.13, 1.86)
157/764
49/1225
206/1989
172/1691
49/406
221/2097
59/395
11/597
70/992
62/844
14/200
76/1044
1.38 (1.05, 1.81)
2.17 (1.14, 4.14)
1.50 (1.17, 1.93)
1.38 (1.05, 1.83)
1.72 (0.98, 3.05)
1.45 (1.13, 1.86)
157/764
49/1225
206/1989
172/1691
49/406
221/2097
bolus reduces risk bolus increases risk
.
.
.
Lactate:
> 5 mmol/L
<= 5 mmol/L
Subtotal (I-squared = 39.2%, p = 0.200)
Period:
before amendment
after amendment
Subtotal (I-squared = 0.0%, p = 0.498)
1.38 (1.05, 1.81)
2.17 (1.14, 4.14)
1.50 (1.17, 1.93)
1.38 (1.05, 1.83)
1.72 (0.98, 3.05)
1.45 (1.13, 1.86)
157/764
49/1225
206/1989
172/1691
49/406
221/2097
59/395
11/597
70/992
62/844
14/200
76/1044
1.38 (1.05, 1.81)
2.17 (1.14, 4.14)
1.50 (1.17, 1.93)
1.38 (1.05, 1.83)
1.72 (0.98, 3.05)
1.45 (1.13, 1.86)
157/764
49/1225
206/1989
172/1691
49/406
221/2097
bolus reduces risk bolus increases risk

33. Back to the drawing board…

34. Fluid is a drug

35. Fluid resuscitation guidelines

36. Response to fluid loading in severe
malnutrition(AFRIM)
And MAPS study
Dr Nchafatso Obonyo
• Management of Paediatric Shock
– Observational study in severe malnutrition:
• Myocardial and haemodynamic response to bolus fluid
resuscitation (current WHO treatment guideline)
• Risk factors for myocardial dysfunction
– Non-malnourished children:
• Gastroenteritis and dehydration + hypovolemic shock
• Severe febrile illness and septic shock (FEAST trial criteria)
• One-year Fellowship in Global Health

38. Other conditions: fluid bolus
Severe Gastroenteritis
Malnutrition
Surgical Burns

39. Myocardial Function
in severe malnutrition
Bernadette Brent
• Detailed assessment comprising:
– Clinical examination
– ECG (including holter ECGs over 7 days)
– ECHO
• Assessment time points:
– Admission
– Day 7
– Day 28
– Any deterioration
– Any IV fluids

40. Summary
Shock present?
20 mls/kg 0.9% saline rapidly, repeat x 2
Rehydration: Plan C
<30ml/kg over 1 hr then 70ml/kg over 3
hrs Ringers Lactate (or 5 hrs if <12m)
(no subtraction of bolus volume)
Overall
No shock: 100 mls/kg ~ 3-5 hrs;
If shock present: 120-160mls/kg ~ 4-5 hrs
(approximately 2-3 times a child’s
circulating volume).
6 hours: If still dehydrated: Restart Plan C

41. FEAST wins Paper of the Year

42. Research- policy pipeline:
Fluid resuscitation as a supportive therapy
Clinical Investigative Clinical trials New Evidence ? PolicyClinical Investigative Clinical trials New Evidence ? Policy
NEJM paper Acidosis Hypovolaemia Clinical trialsNEJM paper Acidosis Hypovolaemia Clinical trials
1996 1997 2000- 2009 FEAST 2011 Trial stopped
WT project grant

43. 2013
EDITION
GUIDELINESFORTHEMANAGEMENTOF
COMMONCHILDHOODILLNESSES
Second edition
POCKET BOOK
OF
Hospital care
for children
2013: Fluid Boluses continue to be
recommended in WHO guidelines

44. Annual excess mortality of boluses predicted per 1 million doses
Kiguli et al , BMJ 2014
5, 200- 132, 000 excess deaths/year for 4 million fluid boluses in children
with severe malaria whilst WHO continue to recommend boluses

45. Time for a bit of knowledge
translation?
Lancet January 2014

47. Future trials……..

48.  Fluids
FEAST trial
Glycaemic controlTransfusion:
TRACT trial
Oxygen
COAST trial
The Silent emergency
Simple treatments: evidence base?
Antibiotics
 Antimalarials
AQUAMAT trial

49. Factorial design: 3950 children
with severe anaemia
•Transfusion strategies
•Long-term management
MalawiUganda
TRansfusion and TReatment of severe Anaemia
in African Children Trial

50. Children’s Oxygen Administration
Strategies Trial (COAST)
PI: Kath Maitland
!
Uganda
Niger
Innovations: ‘Frugal’ technologies
High Flow (PEP): sustainable resource for
respiratory support
John Fraser
Fisher and Paykel
Brisbane Respiratory Group
Kathy Rowan

51. POST: First patient enrolled
EIT: lung recruitment of
oxygenation strategies

52. Clinical trials platform: Added value
Clinical trials facility
GCP compliant trials
East African collaborative
research & capacity buildingLinked sample collection:
basic research